title: Impact of physicochemical properties of engineered fullerenes on key biological responses.
abstract: Engineered fullerenes are widely integrated into several commercial and medical products and are now also being recognized as byproducts of many industrial activities. For most applications fullerenes have to be chemically modified. Surface modification of fullerenes can potentially impact their effect on biosystems. The purpose of the current study was to establish criteria to correlate fullerene structure to biological responses. We report studies of cellular responses induced by three different types of fullerenes that provide varying chemical and physical properties such as electronic behavior, solubility, and degree of agglomeration. Using a systematic and multipronged approach for material characterization and employing critical biological endpoints, we determined the impact of the physicochemical properties of fullerenes on cellular interactions. We examined the ability of these fullerenes to regulate intracellular oxidative stress, necrosis and apoptosis in human monocytic THP1 cells. Results indicate that the carboxylate derivatization of fullerenes was the determining factor in their ability to induce apoptosis. In contrast, the dispersion characteristics of fullerenes were found to be more relevant when considering their redox function. We also established a significant role for functionalization-dependent fullerene-regulation of the caspase proteases in the elicited responses. In addition, there was a notable increase in the level of several anti-oxidant enzymes. Collectively, the results clearly indicate that the physicochemical properties of fullerenes significantly influence the elicited biological response, thus impacting future applications. This study is an initial effort to lay the groundwork for routine correlation and predictive analysis on engineered fullerenes, thus expediting their use.
authors.affiliation: B-7, Bioscience Div, Los Alamos National Laboratory, Los Alamos, NM 87545, USA.
authors.forename: Martin
authors.initials: M
authors.lastname: Rebecca
authors.forename: Wang
authors.initials: W
authors.lastname: Hsing-Lin
authors.forename: Gao
authors.initials: G
authors.lastname: Jun
authors.forename: Iyer
authors.initials: I
authors.lastname: Srinivas
authors.forename: Montaño A
authors.initials: MA
authors.lastname: Gabriel
authors.forename: Martinez
authors.initials: M
authors.lastname: Jennifer
authors.forename: Shreve P
authors.initials: SP
authors.lastname: Andrew
authors.forename: Bao
authors.initials: B
authors.lastname: Yuping
authors.forename: Wang
authors.initials: W
authors.lastname: Chun-Chih
authors.forename: Chang
authors.initials: C
authors.lastname: Zhong
authors.forename: Gao
authors.initials: G
authors.lastname: Yuan
authors.forename: Iyer
authors.initials: I
authors.lastname: Rashi
mesh_terms: D000975:Antioxidants / Q000378:metabolism; D017209:Apoptosis / Q000187:drug effects*; D002264:Carboxylic Acids / Q000737:chemistry; D002460:Cell Line; D004563:Electrochemistry; D037741:Fullerenes / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D009000:Monocytes / Q000187:drug effects* / Q000378:metabolism; D009336:Necrosis / Q000139:chemically induced*; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000187:drug effects*; D012995:Solubility; D013499:Surface Properties
chemical_list: D000975:Antioxidants; D002264:Carboxylic Acids; D037741:Fullerenes